073 Molecular Epidemiology of Epidermolysis Bullosa in a Middle Eastern Population

Epidermolysis bullosa (EB) manifests with skin and mucosal blistering due to mutations in genes encoding components of the cutaneous basement membrane. A thorough knowledge of the region-specific EB subtype and mutation distribution is critical for efficient and population- tailored diagnostics. We ascertained a cohort of 148 Middle Eastern EB patients of various ethnic backgrounds. EBS, JEB, DEB and KEB represented 65, 13.5, 19 and 2.5% of the cohort, respectively. Pathogenic variants were identified in most EB-associated genes. KRT14 and KRT5 mutations were most common among EBS patients (45 and 47% respectively; 13.6% carrying KRT14 bi-allelic mutations). One case of di-genic KRT14 and KRT5 inheritance was identified. Mutations in COL17A1 and laminin 332-encoding genes were identified in 45 and 55% of JEB patients. EB features were evident at birth in 52, 92, 81 and 100% of EBS, JEB, DEB and KEB cases. Although nail dystrophy was uncommon at birth in all EB patients, it was evident in most JEB and DEB patients later in life. Alopecia and EB nevi were uncommon among EBS and JEB cases carrying mutations in laminin 332-encoding genes, however two thirds and 44.4% of patients carrying COL17A1 mutations displayed scarring alopecia (p<0.01) and non-scarring alopecia (p<0.05), respectively while 55.6% of patients carrying COL17A1 mutations developed EB nevi (p<0.05). Carries/teeth loss were evident in two thirds of patients carrying COL17A1 mutations and in only 18.2% of patients carrying mutations in genes encoding laminin 332 (p<0.05). To our knowledge, this is the largest cohort study of EB in the Middle Eastern population which demonstrates that the molecular epidemiology of EB in the Middle East is different from that previously delineated in Europe and the US.